de Melo-Braga Marcella Nunes, Moreira Raniele da Silva, Gervásio João Henrique Diniz Brandão, Felicori Liza Figueiredo
Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.
J Venom Anim Toxins Incl Trop Dis. 2022 Apr 15;28:e20210047. doi: 10.1590/1678-9199-JVATITD-2021-0047. eCollection 2022.
Accidents with venomous animals are a public health issue worldwide. Among the species involved in these accidents are scorpions, spiders, bees, wasps, and other members of the phylum Arthropoda. The knowledge of the function of proteins present in these venoms is important to guide diagnosis, therapeutics, besides being a source of a large variety of biotechnological active molecules. Although our understanding about the characteristics and function of arthropod venoms has been evolving in the last decades, a major aspect crucial for the function of these proteins remains poorly studied, the posttranslational modifications (PTMs). Comprehension of such modifications can contribute to better understanding the basis of envenomation, leading to improvements in the specificities of potential therapeutic toxins. Therefore, in this review, we bring to light protein/toxin PTMs in arthropod venoms by accessing the information present in the UniProtKB/Swiss-Prot database, including experimental and putative inferences. Then, we concentrate our discussion on the current knowledge on protein phosphorylation and glycosylation, highlighting the potential functionality of these modifications in arthropod venom. We also briefly describe general approaches to study "PTM-functional-venomics", herein referred to the integration of PTM-venomics with a functional investigation of PTM impact on venom biology. Furthermore, we discuss the bottlenecks in toxinology studies covering PTM investigation. In conclusion, through the mining of PTMs in arthropod venoms, we observed a large gap in this field that limits our understanding on the biology of these venoms, affecting the diagnosis and therapeutics development. Hence, we encourage community efforts to draw attention to a better understanding of PTM in arthropod venom toxins.
有毒动物引发的事故是一个全球性的公共卫生问题。涉及这些事故的物种包括蝎子、蜘蛛、蜜蜂、黄蜂以及节肢动物门的其他成员。了解这些毒液中蛋白质的功能对于指导诊断和治疗非常重要,此外,这些蛋白质还是多种生物技术活性分子的来源。尽管在过去几十年里,我们对节肢动物毒液的特性和功能的理解不断发展,但这些蛋白质功能的一个关键主要方面——翻译后修饰(PTMs),仍然研究不足。对这些修饰的理解有助于更好地理解中毒的基础,从而提高潜在治疗毒素的特异性。因此,在本综述中,我们通过访问UniProtKB/Swiss-Prot数据库中的信息,包括实验和推测性推断,揭示节肢动物毒液中的蛋白质/毒素翻译后修饰。然后,我们将讨论集中在目前关于蛋白质磷酸化和糖基化的知识上,突出这些修饰在节肢动物毒液中的潜在功能。我们还简要描述了研究“PTM-功能-毒液组学”的一般方法,这里指的是将PTM-毒液组学与PTM对毒液生物学影响的功能研究相结合。此外,我们讨论了涵盖PTM研究的毒素学研究中的瓶颈。总之,通过挖掘节肢动物毒液中的PTM,我们发现在这个领域存在很大差距,这限制了我们对这些毒液生物学的理解,影响了诊断和治疗方法的开发。因此,我们鼓励大家共同努力,以更好地理解节肢动物毒液毒素中的PTM。